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Biomedical subjects

G W Boehm

Publications and source records attributed to G W Boehm.

13 recordsLinked to original sources

Chemical sympathectomy alters numbers of splenic and peritoneal leukocytes.

Sympathectomy of BALB/c mice that were injected with either Listeria monocytogenes or saline did not affect the total number of splenic leukocytes measured 1-3 days after injection, but sympathectomy did increase the percentages of neutrophils in the spleens of both infected and uninfected mice. By contrast, sympathectomy was associated with increased numbers of peritoneal exudate cells (PEC) and peritoneal macrophages in both groups of mice. Sympathectomy did not affect tumor necrosis factor-alpha, interleukin-12, or interferon-gamma production in cultured splenocytes or PEC in either infected or uninfected mice.

Animals↗

Chemical sympathectomy increases numbers of inflammatory cells in the peritoneum early in murine listeriosis.

Here, we investigated the effects of sympathectomy on systemic bacterial loads following infection with Listeria monocytogenes, and on innate and specific immune responses in the peritoneum. Sympathectomy decreased systemic bacterial loads, and increased the number of peritoneal leukocytes and the percentage of peritoneal macrophages three days postinfection. This suggests that sympathectomy-induced decreases systemic bacterial loads are associated with increased recruitment of inflammatory cells into tissues during the innate immune response.

Animals↗

Chemical sympathectomy increases the innate immune response and decreases the specific immune response in the spleen to infection with Listeria monocytogenes.

Many investigators have shown that ablation of the sympathetic nervous system (SNS) with 6-hydroxydopamine (6-OHDA) can alter cell-mediated and humoral immune responses to antigenic challenge. Fewer studies have examined 6-OHDA-induced changes in natural immunity. In this study, we have examined the effect of chemical sympathectomy on the nonspecific and specific phases of the response to infection with Listeria monocytogenes. Sympathectomy decreased splenic bacterial loads 3 and 5 days post-infection and increased splenic neutrophils 3 days post-infection. Sympathectomy decreased splenocyte numbers and antigen-stimulated cytokine secretion from splenocytes. These results suggest that the SNS influences specific responses by modulating innate responses.

Animals↗

One-trial conditioning of the antibody response to hen egg lysozyme in rats.

In Wistar rats, reexposure to a novel conditioned stimulus (CS) previously paired with a protein antigen, hen egg lysozyme (HEL) on a single conditioning trial increased anti-HEL IgG levels relative to conditioned rats that were not reexposed to the CS, conditioned rats that were preexposed to the CS, and nonconditioned rats. These results confirm previous findings that a single exposure to a CS associated with immunization is sufficient to elicit an antibody response upon subsequent reexposure to the CS in the absence of exogenous antigen.

Animals↗

Moderate exercise is associated with enhanced antigen-specific cytokine, but not IgM antibody production in aged mice.

It has been suggested that moderate exercise may modulate the immune response in the elderly. We investigated whether moderate exercise had an effect on the immune response to viral infection in both young (2-4 months) and older (16-18 months) male BALB/cJ mice. Exercised (EX) mice ran on a treadmill for 8 weeks at a gradually increasing speed and duration whereas control (CON) mice were only handled briefly during each exercise session and then returned to their cages. Mice were infected with herpes simplex virus type 1 (HSV-1) 24 h post-exercise. Serum IgM anti-HSV antibody, HSV-1 specific Th1/Th2 cytokine production by spleen cells, and cytokine production by alveolar cells were measured 7 days post-infection. In the aged mice, exercise was associated with an enhanced production of the HSV-1 specific Th1-associated cytokines, interleukin (IL)-2 and interferon (IFN)-gamma, but had no effect on the Th2-associated cytokine IL-10 or IgM antibody. No effect of exercise was observed in young mice. IL-12 production was not altered by exercise, but aging was associated with altered IL-12 production in a tissue-specific manner. In conclusion, moderate exercise was associated with increased antigen-specific IL-2 and IFN-gamma production in response to viral challenge in older mice.

Aging↗

Prolonged exercise suppresses antigen-specific cytokine response to upper respiratory infection.

Fatiguing exercise has been associated with an increased susceptibility to infection. This study examined the antigen-specific T-helper (Th) type 1 and Th type 2 cytokine response to herpes simplex virus (HSV) infection after an acute bout of fatiguing exercise. Male BALB/cJ mice ran on a treadmill (Ex) until voluntary fatigue (approximately 2.5 h), and control mice were handled and remained next to the treadmill. Mice were infected with HSV 20 min after exercise. Mice were killed 2 or 7 days postinfection, and sera and spleens were taken for the determination of HSV-specific serum IgM, splenocyte cytokine production during culture with HSV, and splenocyte natural killer cell cytotoxicity. Both Th type 1 [interleukin (IL)-2, interferon-gamma, IL-12] and Th type 2 (IL-10) cytokine production in spleen cell cultures, as well as natural killer cell cytotoxicity, decreased in Ex on day 2 postinfection. On day 7 postinfection, there was no difference in HSV-specific serum IgM or cytokine production by cells from control and Ex mice, with the exception of decreased IL-12 in Ex mice. These findings suggest that fatiguing exercise may alter the kinetics of antigen-specific cytokine production.

Animals↗

Learning in year-old female autoimmune BXSB mice.

BXSB/ MpJ-Yaa and NZB/BINJ mice have been used as animal models for both developmental learning disability and systemic autoimmune disease. Approximately 40-60% of these animals show ectopic clusters of neurons in Layer I of cortex similar to those found in postmortem analyses of human dyslexics, and all exhibit an autoimmune condition similar to systemic lupus erythematosus (SLE) in humans. The expression of immune disease in the BXSB strain, unlike in humans, is more severe in males than females. Most previous studies have examined the behavioral sequelae of neocortical ectopias at a relatively young age, when the BXSB females (unlike the male BXSB and female and male NZBs) are not yet showing high titers of autoantibodies associated with their lupus-like form of autoimmune disease. This study examined the behavior of BXSB females at an age subsequent to autoimmune disease onset. When contrasted with younger animals, year-old BXSB females showed good learning behavior, with no differences in Lashley maze learning and remarkably good performance in a visual discrimination learning task. These results are consistent with other data which indicate that many types of learning behavior are apparently unperturbed by systemic autoimmune disease. Results also showed significant interactions between a measure of lateral paw preference and the presence or absence of ectopias in Lashley maze learning. Animals without ectopias that exhibited a right lateral paw preference showed the greatest number of errors on a number of test measures. These findings support previous results indicating that behavioral effects associated with ectopias may vary based upon the behavioral laterality of affected animals.

Age Factors↗

Learning and memory in the autoimmune BXSB mouse: effects of neocortical ectopias and environmental enrichment.

Approximately 40-60% of BXSB mice have ectopic cell clusters in layer 1 of neocortex. Prior studies have shown distinct behavioral differences between those with ectopias and their non-ectopic littermates. In this study, female BXSB mice were reared after weaning in either enriched environments or standard cages. Following an initial round of behavioral testing, all mice were housed in standard cages and retested. Enriched cage mice (both ectopic and non-ectopic) showed increased activity, greater speed, and enhanced learning scores across a variety of tests. Additionally, prior test experience itself had significant positive effects on Hebb-Williams maze learning. The presence of ectopias resulted in better Morris maze learning for standard cage reared mice. Further, ectopic mice, regardless of their housing condition, showed better long-term retention in the Morris maze than did their non-ectopic counterparts. These findings show that abnormalities in corticogenesis need not always result in functional deficit.

Analysis of Variance↗

Effects of embryo transfer and cortical ectopias upon the behavior of BXSB-Yaa and BXSB-Yaa + mice.

The BXSB-Yaa and BXSB-Yaa + inbred strains of mice differ primarily with respect to the Y chromosome, although there is evidence that they differ on several autosomal genes as well. Each strain has ectopic collections of neurons in neocortical layer I (ectopias), with a higher occurrence in males (58%) than females (42%). Conventionally reared mice from these strains were compared to mice that were transferred, as 8-cell embryos, into the uteri of non-autoimmune recipients, who gave birth to and reared the offspring. The transfer procedure did not change the incidence of ectopias in either sex. There were, however, major differences in behavior. Compared to conventionally reared controls, embryo transfer mice had greater behavioral asymmetry, poorer performance in a black-white discrimination, poorer Morris maze learning, better Lashley maze learning, and better performance in a two-way shuttlebox. Within the transfer groups, females differed as much as males, confirming our prior findings and supporting our thesis that the two strains differ on several autosomal genes in addition to the Y chromosome. These findings show that the intra-uterine environment can powerfully and selectively affect later behavior. When ectopic and non-ectopic mice were compared, BXSB-Yaa mice with neocortical ectopias were better able to learn the Morris spatial maze than non-ectopic controls; this was true whether the mice were conventionally reared or embryo transferred. In contrast, BXSB-Yaa + ectopic mice did not differ from their controls if conventionally reared, but were much worse than controls if embryo transferred.

Animals↗

A computer-aided procedure for measuring Hebb-Williams maze performance.

We describe a shortened procedure for testing mice over a 5-day interval on a swimming version of the Hebb-Williams maze. The mice are given 1 day of adaptation training, and are tested over the next 4 days on Hebb-Williams problems 1, 6, 12, and 5, in that order. As an animal swims through one of the maze problems, the computer screen shows the maze pattern, and an observer traces the path taken with a computer mouse. The computer program, Observe Software, stores the path sequence, determines the error score for that trial, and sends the information to a spreadsheet where it is available for statistical analyses.

Animals↗

Sex differences in the distribution of axon types within the genu of the rat corpus callosum.

Neuroanatomical sex differences have been documented in the rat neocortex, including dimorphism of its predominant commissure, the corpus callosum (CC). In particular, CC sex differences have been reported in the ultrastructure of the posterior callosal region, the splenium. Since the CC is a heterogeneous fiber tract with its axons arising from distinct cortical areas and passing through restricted regions along its length, it became of interest to ascertain whether cellular sexual dimorphisms may also be present in another division of the CC. To test this hypothesis, electron microscopy was used to examine axon composition in adult male and female rats in the anterior portion, the genu. The number and size of axons, the thickness of the myelin sheath, and the area within the genu occupied by these constituents, were quantified. Results showed a significant sex difference in the ratio of unmyelinated to myelinated axons, with females having a larger proportion of unmyelinated fibers. This effect was present for both (1) the number of axons, and (2) the area taken up by axonal fibers. No differences were found in the size of either axon type, or for myelin thickness. Comparison of these results with those from the splenium and possible mechanisms underlying this dimorphism are discussed.

Analysis of Variance↗

Behavior, cortical ectopias, and autoimmunity in BXSB-Yaa and BXSB-Yaa+ mice.

The BXSB-Yaa recombinant inbred strain was created by crossing a male SB/Le with a female C57BL/6J. A Y chromosome factor derived from the SB/Le male, known as the autoimmune accelerator (Yaa), leads to an earlier onset and greater severity of autoimmune disease in males. In contrast, male BXSB mice, which lack the Yaa gene (called BXSB-Yaa+) because their Y chromosome is derived from the C57BL/6J, do not develop an autoimmune condition. To examine the influence of the Y chromosome on behavior, cortical ectopia incidence, and immune functioning, males and females of these two strains were compared. Significant strain differences (for both sexes) were found for behavioral measures including discrimination, spatial and avoidance learning, and activity. For immunological parameters, a sex difference was seen in the BXSB-Yaa (males more autoimmune), but not in the BXSB-Yaa+ strain. As expected, male BXSB-Yaas were more autoimmune than male BXSB-Yaa+s. However, there was also a strain difference for IgG in the females (BXSB-Yaa+ greater). No strain difference was found for the presence of ectopias. However, there was a sex difference across both strains, with males having a higher incidence. BXSB-Yaa and BXSB-Yaa+ mice have behavioral and immunological differences greater than would be predicted by their known genetic differences. The significant differences between the two female groups suggest that the two strains differ with respect to autosomal genes, in addition to the Y chromosome. The incidence of ectopias is independent of this genetic difference and is influenced by the subject's sex.

Animals↗

Neocortical ectopias in BXSB mice: effects upon reference and working memory systems.

BXSB mice have an approximately 40-60% incidence of neocortical ectopias in layer I of the prefrontal/motor cortex. Prior studies have found major behavioral differences between those with ectopias and their non-ectopic littermates. Some of these findings indicate that the two groups differ with respect to spatial reference and working memory. The purpose of this study was to measure reference and working memory in the same animals to test the hypothesis that the ectopics would have better reference memory but less effective working memory. The Lashley III maze has cul-de-sacs which must be eliminated, and T-choices where the animal has to decide whether to go left or right. Ectopic and non-ectopic mice were equally able to learn the maze and did not differ on cul-entry or T-choice errors. Then the maze was inverted and the animals were retested. Turning the maze upside down did not change the relative status of the blind alleys. Therefore, the reference memory knowledge from the prior week's training could be used to avoid entering the culs. However, inverting the maze caused a left-right mirror image reversal of the T-choices. Therefore, prior reference memory information would interfere with learning the new path through the maze, whereas working memory would enable the mouse to eliminate T-choice errors. Ectopic mice made less cul-entry errors and more T-choice errors than their non-ectopic littermates, as predicted.

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